DESCRIPTION: (Principal Investigator's Abstract) This continuing research program remains focused on the development and application of novel synthetic methods. The investigations build on past efforts in which new and efficient synthetic methodologies have been uncovered and applied to the preparation of simple, biomedically important, members of several natural and non-natural product families. In one area, mild oxidative procedures for iminium and oxoniun cation generation have been developed and their utility in promoting efficient Mannich and Prins cyclizations have been demonstrated by applications to stereocontrolled preparation of polyhydroxylated-piperidines and tetrahydro-pyrans and -furans. In future studies, the preparative potential of oxidative methods for oxonium cation generation will be probed further by their use in syntheses of biomedically significant targets in the l-deoxy-C-glycosyl peptide and tetrahydropyran families. Efforts to develop the synthetic potential of an interesting pyridinium salt photocyclization reaction, which efficiently and stereoselectively produces 4-amino-3,5-cyclopentendiol derivatives, will continue. This methodology will be used as the starting point for concise syntheses of selected bioactive members of the aminocyclopentitol, amino-sugar and polyhydroxylated aminocyclohexane families. Lastly, a major effort will be given to the development of novel and potentially general strategies for controlling the absolute and relative stereochemistry of synthetically potent, intramolecular enone-olefin 2+2-photocycloaddition reactions. The foundations of these strategies will be tested in studies of intramolecular 2+2-photoadditions of alpha- and beta-pyrrolidino-cycloalkenones and closely related pyrrolidino-eniminium salts. The preparative power of these methods will be tested by their use in non-racemic syntheses of key intermediates in routes to selected members of the polyquinane and hydoazulene sesquiterpene natural product families.